Silver nanoparticles protect against arsenic induced genotoxicity via attenuating arsenic bioaccumulation and elevating antioxidation in mammalian cells

Abstract Arsenic (As) and its compounds have been classified as Group I carcinogenic agents by the International Agency for Research on Cancer (IARC); however, there is few specific and efficient antidotes used for As detoxification. The present study aimed to investigate the protective effects of silver nanoparticles (AgNPs) at non-toxic concentrations on As(Ⅲ) induced genotoxicity and the underlying mechanism. Our data showed that AgNPs pretreatment significantly inhibited the generation of phosphorylated histone H2AX (γ-H2AX, marker of nuclear DNA double strand breaks) and the mutation frequencies induced by As(Ⅲ) exposure. Atomic fluorescence spectrometer (AFS) and laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) analysis revealed that the intracellular accumulation of As(Ⅲ) in human-hamster hybrid AL cells was declined by AgNPs via suppressing the expression of specific As(Ⅲ)-binding protein (Gal-1). Moreover, the activities of antioxidant enzymes were greatly up-regulated by AgNPs, which eventually inhibited the generation of reactive oxygen species (ROS) induced by As(Ⅲ) and the downstream stress-activated protein kinases/c-Jun amino-terminal kinases (SAPK/JNK) signaling pathway. These results provided clear evidence that AgNPs dramatically suppressed the genotoxic response of As(Ⅲ) in mammalian cells via decreasing As(Ⅲ) bioaccumulation and elevating intracellular antioxidation, which might provide a new clue for AgNPs applications in As(Ⅲ) detoxification.